tbuckley/cabot-search huggingface dataset:
Abstract 14: Infant Gut Microbiome is Associated With Child Blood Pressure at Age 3 and 6 Years: Findings From a Danish Birth Cohort
Authors: Tiange Liu, Jakob Stokholm, Ni Zhao, Noel T Mueller
Journal: Circulation (2023)

Background: Experimental germ-free mice studies indicate that the gut microbiome affects blood pressure (BP). To our knowledge, no epidemiologic studies have investigated whether childhood BP, which portends future cardiovascular disease risk, is influenced by the infant gut microbiome—a microbiome that is less confounded by lifestyle. Understanding the link between gut microbiome and BP will shed light on gut microbiome as a modifiable way to improve child cardiovascular health. Objectives: To examine prospective associations of the gut microbiome at 1 month and 1 year with systolic BP (SBP) at 3 and 6 years, and to examine if the associations differed by breastfeeding duration over infancy. Methods: We used data from children followed up from birth to six years of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort in Denmark. We measured infant gut microbiome at 1mo and 1y by 16S rRNA sequencing (V4 region). Research staff measured child BP in triplicate using standardized protocols during scheduled study visits at 3y and 6y. We analyzed microbiome features at each time point during infancy in relation to SBP at 3y and 6y, separately. We focused on Shannon index as a measure of microbiome alpha diversity, and differential abundance of microbial taxa. We assessed effect measure modification by breastfeeding duration at time of microbiome measurement. We adjusted models for maternal diet score during pregnancy, preeclampsia, gestational age, birth weight, and breastfeeding duration (when it was not a modifier). Results: Of 526 children included in the analysis, 49% were female and 78% were born vaginally. A 1-unit increment in Shannon index at 1mo was associated with -0.35 mmHg (-1.61, 0.91) lower SBP at 3y and -1.21 (-2.20, -0.23) lower SBP at 6y. Lower abundance of Bacteroides and higher abundance of Staphylococcus at 1mo was associated with higher SBP at 3y only (both FDR-P &lt;0.05); no microbial taxa at 1mo were significantly associated with SBP at 6y. As for microbiome at 1y, associations differed by breastfeeding duration ( P-interaction &lt; 0.10). In children who were breastfed beyond 1y, a 1-unit increment in Shannon index at 1y was associated with -2.94 mmHg (-5.59, -0.28) and -1.02 mmHg (-3.24, 1.19) lower SBP at 3y (n=56) and 6y (n=72), respectively. In contrast, in children who were breastfed shorter than 1y, 1-unit increment in Shannon index was associated with 0.55 (-0.75, 1.85) and 1.26 (0.28, 2.24) higher SBP at 3y (n=298) and 6y (n=382), respectively. After multivariable adjustment, no microbial taxa at 1y were significantly associated with SBP at 3y or 6y. Conclusions: Higher gut microbiome Shannon diversity and higher Bacteroides and lower Staphylococcus at 1 month was prospectively associated with higher child BP at 3 and 6 years of age. Microbiome Shannon diversity at 1 year was also associated with child BP, however, associations depended on breastfeeding.
Abstract 37: Proteomic Signatures of Obesity-Related Heart Failure in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Bige Ozkan, Jingsha Chen, Justin B Echouffo Tcheugui, Pascal Schlosser, Kari E North, Kuni Matsushita, Christie M Ballantyne, Bing Yu, Amil M Shah, Elizabeth Selvin, Josef Coresh, Chiadi E Ndumele
Journal: Circulation (2023)

Background: Obesity is a strong risk factor for cardiovascular disease. The excess heart failure (HF) risk associated with obesity is uniquely unexplained by traditional risk mediators. We sought to identify proteomic signatures that reflect mechanistic pathways associated with obesity-related HF. Methods: We quantified 4955 plasma proteins in stored plasma samples of ARIC Visit 2 (1990-1992) participants without HF using an aptamer-based platform (SOMAScan v4.0). We used Cox regression to identify the proteins associated with incident HF, stratified by obesity (BMI≥30 kg/m 2 ). We used Bonferroni-corrected p-values to assess statistical significance in 2/3 discovery and 1/3 validation subsets. We assessed the biological pathways overexpressed by these proteins using a canonical pathway analysis. Results: We included 9940 participants (28% with obesity, mean age 57 years, 55% female, 22% Black adults). Over a median 21-year follow-up, 2,345 HF events (886 in obesity) occurred. In the discovery subset with obesity, we identified 110 proteins associated with incident HF after demographic adjustment, 19 proteins (7 specific to obesity, Figure B) had robust HF associations after additional adjustment for lifestyle and cardiometabolic risk factors (p&lt;10 -5 ) (Figure A). Of 19 proteins, 12 were also linked to prevalent obesity status. Angiopoietin-2 was associated with higher risk of HF and higher odds of obesity. Conversely, ephrin type-A receptor 4 and seizure 6-like protein were linked to lower HF risk and lower odds of obesity. Lipid and bile acid metabolism (inhibited), cytokine signaling and wound healing pathways (activated) were overexpressed by HF-associated proteins in those with obesity. Conclusion: We identified established and novel proteins associated with HF risk in obesity. Many proteins linked to incident HF in obesity are also strongly associated with prevalent obesity. Formal mediation analysis can help elucidate the potential role of these proteins in the development of obesity-related HF.
Abstract P232: Associations Between Park Acreage and Physical Activity Among Adolescents Living in Urban Green Cities: Exploring the Concept of a Park Oasis
Authors: Eydie N Kramer-Kostecka, Sarah Espinoza, Junia de Brito, Daheia Barr-Anderson, Jaime Slaughter-Acey, Eydie Kramer-Kostecka
Journal: Circulation (2023)

Introduction: Regular participation in physical activity (PA) improves cardiovascular health outcomes across the lifespan. Previous research has established a relationship between park access (i.e., distance to parks) and youth PA; however, no studies have examined the associations between park acreage and PA among youth living in “green” cities (i.e., residents can access parks via a 10-minute walk). Purpose: The present study examined how park acreage is related to PA among adolescents living in two urban green cities: Minneapolis and St. Paul, MN. Further, a “park oasis” was conceptualized. Methods: Data were drawn from a large, population-based cohort study (Project EAT 2010; Eating and Activity in Teens). Geospatial analyses determined park access and acreage variables associated with respondents’ home addresses. Study analyses were cross-sectional, and restricted to those with adequate park access, as indicated by living within 800-meters of a park (n=2,271; mean age=14.5±1.9 years; 52.9% female; 82.8% Black, Indigenous, Person of Color). Multivariable linear regression models were used to examine the associations between park acreage and PA, adjusted by individual (e.g., race/ethnicity) and structural (e.g., neighborhood poverty) variables. Park acreage was examined as a continuous (% land-use within a 3000-meter network buffer of home address) and a categorical variable based on park land-use % cut-points (Groups 1-4). Results: In unadjusted models, continuous park acreage was positively associated with both total PA (p=.020) and moderate-vigorous PA (MVPA; p=.007). Also in unadjusted models, categorical park acreage was significantly, positively associated with PA outcomes, with Group 1: Park Oasis appearing optimal. All adjusted models were non-significant. Conclusions: Findings indicate that park acreage may be an important PA facilitator among adolescents. Future work should explore how individual and structural factors relate to PA outcomes and inequitable allocation of parkland.
Abstract 55: Racial/Ethnic Disparities in Sleep Outcomes Among Adults With Hypertension in the 2011-2018 National Health and Nutrition Examination Survey
Authors: Faith E Metlock, Thomas Hinneh, Oluwabunmi Ogungbe, Xiaoyue Liu, Sabrina d Elias, Binu Koirala, Cheryl R Dennison Himmelfarb, Yvonne Commodore-Mensah
Journal: Circulation (2023)

Introduction: Ethnic/racial minority groups in the US bear a disproportionate burden of hypertension (HTN). Given the association between poor sleep outcomes and HTN, we examined racial disparities differences in sleep outcomes among persons adults living with HTN in the US. Methods: We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (2011-2018) . Sleep outcome variables were examined via self-report questionnaires as daytime sleepiness (no/mild/and excessive), sleep duration (recommended 7-9 hours/short ≤6 hours/and long &gt;9 hours), sleep quality (good/ or poor). Multinomial logistic regression models were used to assess the association between race/ethnicity categories (Non-Hispanic White Americans [NHW], Non-Hispanic Black Americans [NHB], Non-Hispanic Asian Americans [NHA], and Mexicans/Hispanic Americans) and sleep outcomes, adjusting for covariates. Results: In a sample of 10,934 adults diagnosed with HTN (with mean age 58 (±16) years; and 48% female); prevalence of short sleep duration (≤ 6 hours) among NHW, NHB, NHA, and Mexicans/Hispanic Americans were 55%, 21%, 5%, and 14%, respectively. While the odds of abnormal daytime sleepiness (mild and excessive) were lower across all race/ethnic categories compared to NHW; the odds of short sleep duration were higher among NHB (adjusted odds ratio [aOR]:= 2.02; 95% confidence interval [CI]: 1.53-2.65). Similarly, the odds of poor sleep quality were higher among NHA (aOR: 1.90; 95% CI: 1.24-2.91) and Mexicans/Hispanic Americans (aOR: 1.66; 95% CI: 1.21-2.28). Conclusion: Significant racial disparities exist in sleep outcomes among adults with HTN in the US. Efforts to improve equity in HTN and CVD prevention and management must also address sleep outcomes.
Abstract 46: MIND Diet-Related Transcriptomic Alterations in the Aging Human Brain is Associated With Lower Dementia Risk and Slower Cognitive Decline
Authors: Jun Li, Ana Capuano, Puja Agarwal, Yanling Wang, Philip De Jager, Zoe Arvanitakis, David Bennett, Liming Liang, Francine Grodstein
Journal: Circulation (2023)

Background: Healthy diets are associated with lower dementia risk; however, the underlying molecular mechanisms are largely unknown. Hypothesis: A healthy diet is associated with brain transcriptomic alterations that are related to a better cognitive health. Methods: RNA sequencing was conducted using dorsolateral prefrontal cortex from 1,204 deceased participants of the Religious Orders Study and Rush Memory and Aging Project. Annual cognitive/clinical assessments were performed from enrollment through death. Diet was assessed at baseline/follow-ups in 482 individuals using a validated food-frequency questionnaire. Among these individuals, we calculated a MIND diet score ( M editerranean-DASH Diet I ntervention for N eurodegenerative D elay) to assess intakes of a presumed neuroprotective diet pattern, and applied elastic net regression to identify a brain transcriptomic profile associated with the MIND diet. Results: In individuals with dietary data (n=482), we identified a transcriptomic profile, consisting of 50 genes, for the MIND diet; the profile score was significantly correlated with MIND diet score ( r =0.15; P =0.001). In multivariable analyses of the remaining 722 independent individuals, a higher transcriptomic profile score was significantly associated with lower odds of dementia (OR=0.76 per SD increment in transcriptomic score; P =0.003) and slower annual rate of decline in global cognition (β=0.011; P =0.004). In secondary Mendelian randomization analysis, genetically predicted MIND diet-transcriptomic profile score was associated with lower Alzheimer’s dementia risk (OR=0.93; P =0.04), but not vice versa. Conclusion: MIND diet was associated with gene expressions in the human brain that were related to less dementia and cognitive decline. Associations did not appear due to reverse causation. Our findings suggest that associations between diet and brain health may involve molecular alterations at the transcriptomic level; and may inform future therapeutics design for dementia prevention.
Abstract P275: Mediterranean Dietary Pattern Assessment and Cardiac Health in Firefighters
Authors: Deborah L Feairheller
Journal: Circulation (2023)

Nutritional epidemiology is faced with the challenge of estimating overall diet quality and adherence, along with how this relates to health outcomes. Several dietary assessment tools exist for the Mediterranean dietary pattern. Additionally, we recently validated a clinical study Mediterranean Diet Scoring System (MDSS). Firefighters are a population that faces additional challenges. The leading cause of mortality in firefighters remains cardiovascular, so improving diet is important. Our prior studies have found that blood pressure (BP) surges that firefighters experience are dependent on call type and occupational activity and that firefighters are interested in learning healthy dietary patterns. The purpose of this pilot study was to compare the PREDIMED study screener, MEDI-Lifestyle score, and MDSS. A secondary purpose was to examine relationships between these scores with health outcomes. 15 firefighters (36.3±9.5 yrs) completed surveys, a health history, and a 6-week Mediterranean diet and tactical training intervention. Physiological testing included BP, BMI, ambulatory BP monitoring during a 12-hr work-shift, and fitness testing. Each firefighter was assigned a wellness coach who provided weekly dietary training, answered questions, and tracked diet and exercise progress throughout. Data was self-reported by firefighters through a clinical study website. Firefighters had elevated BP (128.7±9.4 /77.6±7.0 mmHg), overweight BMI classification (29.9±3.2 m/kg 2 ), and low fitness (VO 2 30.1±4.4 ml/kg-min). Firefighters scored low on all scales with MEDI-Lifestyle score of 2.9±1.0 out of 7, a PREDIMED score of 6.3±2.3 out of 14, and overall MDSS of 67.1±16.8 out of 102 possible points. We found direct relationships between the screening tools, but sample size is too small to establish significance. MEDI-Lifestyle (r = -0.44) and MDSS (r = -0.6) were inversely related to depression scores (p&lt;.05). MDSS was inversely related to SBP surge with fire-calls (r = -0.6, p&lt;.05). During the work-shift, firefighters experienced BP levels in the hypertensive range (145.5±14.1 /87.8±15.8 mmHg) and extreme BP surges when alarms sounded (21.6±11.8 /15.2±12.8 mmHg). Firefighters with higher DBP had higher overall ambulatory BP levels (r = 0.7, p&lt;.01), higher BP surges (r=0.6, p&lt;.05), and higher overall occupational BP levels (r = 0.7, p&lt;.01). It seems that multiple screening tools are effective at assessing a Mediterranean dietary pattern. Further research is needed to examine dietary adoption and related health outcomes in firefighters. A full study is needed to better understand the relationship between different Mediterranean diet screeners. Furthermore, it needs to be investigated where the relationship lies with DBP and overall cardiac health in firefighters. Subclinical diastolic dysfunction may exist and if undiagnosed, it could lead to cardiac incidents.
Abstract 22: The Effects of Randomized Cocoa Extract and Multivitamins on the Gut Microbiome: A Pilot Study in COSMOS
Authors: Yanbin Dong, Jun Li, Haidong Zhu, Li Chen, Kyu H Lee, Joann E Manson, Howard D Sesso
Journal: Circulation (2023)

Background: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a recently completed randomized, double-blind, placebo-controlled, 2x2 factorial trial of a multivitamin and cocoa extract supplement (containing 500 mg/d flavanols) in 21,442 older adults. In view of favorable effects of multivitamins on cognition and promising signals for cardiovascular risk reduction with cocoa extract, we conducted a pilot study to explore whether these interventions affected gut microbial composition and function. Methods: We conducted deep shotgun metagenomic sequencing in 30 COSMOS participants using fecal samples collected at baseline and year 2. We performed taxonomic profiling using MetaPhlAn2 and functional profiling using HUMAnN2. After proper quality filtering, we analyzed effects of both interventions on 2-year changes in microbial features, adjusting for age, sex, and body mass index. Results: Cocoa extract supplementation significantly altered the overall gut microbial taxonomic compositions from baseline to year 2, and explained 5.5% of the variance in the 2-year changes in relative abundance of all microbial species ( P =0.008). We further found that randomized cocoa extract supplementation altered the relative abundance of a few microbial species, including those previously linked to anti-inflammatory and cardiometabolic benefits (e.g., Akkermansia muciniphila , nominal P &lt;0.05), and several microbial super pathways (including pyrimidine ribonucleotides de novo biosynthesis, FDR=0.03, and 28 other pathways with nominal P &lt;0.05). Randomized multivitamin use did not significantly affect 2-year changes in alpha or beta diversity, but altered the abundance a few putative bacterial species and functional pathways (nominal P &lt;0.05). Summary: Our pilot study suggests that cocoa extract and multivitamin supplementation in COSMOS may alter the gut microbiome and influence pathways relevant to health, emphasizing the need for larger studies that allow for more detailed investigations.
Abstract P180: Disparities in Occurrence of Stroke Among Heart Failure Patients- A Case Control Study Evaluating Impact of Community Socioeconomic Distress Index
Authors: Brian Witrick, Frank Annie, Wes Kimble, George Sokos, Christopher Bianco, Sarah Rinehart, Timothy Dotson, Brian Hendricks
Journal: Circulation (2023)

Introduction: Ischemic stroke is common complication among heart failure patients. Community-level socio-economic distress has been linked to adverse clinical outcomes in prior research. However, few to no studies have examined the relationship between neighborhood level socio-economic distress and stroke within a population of heart failure patients exclusively. Hypothesis: Odds of stroke among patients with heart failure are higher in neighborhoods with increased socio-economic distress, controlling for patient demographic and clinical comorbidities. Methods: Two separate cohorts of heart failure patients were assembled using ICD9/10 codes to identify all patients with a heart failure diagnosis seen at West Virginia University Hospital Systems (WVU Medicine) between 2008 and 2020 and Charleston Area Medical Center (CAMC) between 2017 and 2020. Cases were defined as heart failure patients with a diagnosis of ischemic stroke. Controls were defined as heart failure patients without a diagnosis of stroke and were matched to cases 4:1 on five-year age grouping and sex at birth. Distressed communities index (DCI) was linked to clinical data by patient zip code of residence. Neighborhoods with a DCI above 75 were classified as distressed, while those below were noted as non-distressed. Multivariable conditional logistic regression was used to identify significant associations at the 95% confidence level within each cohort separately. Results: In total there were 26,532 unique heart failure patients in the WVU Medicine cohort and 20,070 in the CAMC cohort. Of these, 10.3% (n=2,741) of the WVU Medicine cohort and 4.5% (n=900) of the CAMC cohort met the case definition of having had a diagnosis of stroke. Among patients in the WVU Medicine cohort with heart failure who experienced a stroke, 47.1% (n=1,291) were male and had an average age of 72.4 (± 12.9). In the CAMC cohort, among heart failure patients who experienced a stroke, 51.1% (n=460) were male and the average age was 70.9 (± 11.8). After controlling for demographics and clinical comorbidities, conditional logistic regression analyses identified a statistically significant association between neighborhood-level socio-economic distress in both the WVU Medicine cohort (OR = 1.31; 95% CI = 1.20 - 1.44) and the CAMC cohort (OR = 1.29; 95% CI = 1.027 - 1.454). Conclusion: Neighborhood-level socio-economic distress was associated with prevalence of stroke among heart failure patients. This is a critical finding for rural states, such as West Virginia, as it has the ability to inform placement of new satellite clinics among large hospital systems, or government funded clinics, such as federally qualified health centers, to address inequities in care for patients living in medically underserved communities.
Abstract P554: Association of a Genetic Risk Score With Cholesterol and Cholesterol Control: Findings From the Hispanic Community Heath Study/Study of Latinos
Authors: Christina G Hutten, Tamar Sofer, Molly Scannell Bryan, Jiehuan Sun, Victoria W Persky, Martha L Daviglus, Maria Argos
Journal: Circulation (2023)

Background: Hypercholesterolemia is a prevalent cardiovascular (CVD) risk factor among Hispanics/Latinos; however, rates of cholesterol awareness and treatment are low in this population. Using a genetic risk score (GRS) associated with low-density lipoprotein cholesterol (LDL) levels may help identify those who would benefit most from statin therapy. A 223-SNP GRS was previously shown to be associated with baseline LDL levels and CVD risk in European, African, and East Asian populations, but it was not evaluated for use in a Hispanic/Latino population. Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective study that enrolled 16,415 Hispanic/Latino adults aged 18-74 years from four US communities in 2008-2011. We assessed the association of a 223-SNP GRS with baseline LDL levels and cholesterol control among 8,868 HCHS/SOL participants with complete data and consent to conduct genetic research. A weighted GRS was calculated using effect sizes estimated from the Million Veteran Program Genome Wide Association Study that included about 25,000 Hispanic/Latino participants. Multivariable linear regression analysis was used to derive effect size estimates (Betas (β), 95% confidence intervals (CI)) for the association between the GRS, modeled continuously and by quintiles, and LDL levels. Multivariable logistic regression was used to derive odds ratios and 95% CI for the association between GRS and LDL control in statin users. LDL control was defined as LDL &lt;130mg/dL or &lt;100 mg/dL in those with diabetes. Models were adjusted for predefined confounders and accounted for survey weights. Results: For each standard deviation increase in GRS, LDL levels increased on average by 8.61mg/dL (95% CI 7.37, 9.83) when adjusted by age, sex, and the first 5 principal components. GRS associations with LDL differed by strata of sex, Hispanic/Latino background group, and European genetic ancestry proportion. In 1,114 statin users, odds of cholesterol control were 38% less likely for those in the highest quintile of GRS compared to the lowest quintile, although not significant (OR 0.62, 95% CI 0.36, 1.08). Conclusion: The 223-SNP GRS shows promise to identify those who are more likely to develop higher LDL and may benefit most from statin therapy in a Hispanic/Latino population. However, additional studies are needed in a larger population of Hispanic/Latino statin users for confirmation of these results.